基于网络药理学和分子对接探讨逍遥散抗抑郁的作用机制

Antidepressive mechanism of Xiaoyao powder:A study based on network pharmacology and molecular docking

目的:采用网络药理学和分子对接技术深入研究逍遥散抗抑郁的机制,为临床诊断与治疗提供理论上的依据。方法:首先使用TCMSP检索柴胡、当归、白芍、白术、茯苓、甘草、干姜、薄荷的主要活性成分,并筛选出口服生物利用度≥30%、类药性≥0.18的中药作用靶点,再使用GeneCards、Pharm Gkb、TTD、DrugBank等数据库系统筛选出抑郁症的有关靶点,并获取交集基因,将抑郁症的相关基因与逍遥散的有效活性成分进行交集,最后使用STRING构建蛋白质-蛋白质相互作用(PPI)网络,使用Cytoscape 3.8.0应用软件查找PPI网络系统核心,构建“中药-疾病-靶点”通路,进行基因本体(GO)功能和京都基因与基因组百科全书(KEGG)通路富集分析。最后运用Pymol软件对逍遥散的有效活性成分与抑郁症疾病靶点进行分子对接。结果:获得逍遥散有效活性成分161种;逍遥散抗抑郁靶点2588个,其中核心靶点6个;GO生物过程2247条,KEGG通路179条。分子对接结果显示,逍遥散中柚皮素、利可查尔酮、木犀草素、槲皮素均能较好地与抑郁症靶蛋白结合。结论:逍遥散抗抑郁的潜在药理学机制及其活性化合物可能与细胞增殖、免疫调节和炎症诱导的协同调节有关。

Objective:To investigate the antidepressive mechanism of Xiaoyao powder based on network pharmacology and molecular docking,and to provide a theoretical basis for clinical diagnosis and treatment.Methods:At first,TCMSP was used to search for the main active components of Bupleurum chinense,Angelica sinensis,Radix Paeoniae Alba,Atractylodes macrocephala Koidz.,Poria cocos,Radix Glycyrrhizae,dried ginger,and Mentha haplocalyx,and action targets were obtained for traditional Chinese medicine(TCM)drugs with oral bioavailability≥30%and drug-likeness≥0.18,and then GeneCards,Pharm Gkb,TTD,and DrugBank databases were used to screen for the targets associated with depression;intersecting genes were obtained between depression-related genes and the effective active components of Xiaoyao powder.STRING database was used to construct a protein-protein interaction(PPI)network,and Cytoscape 3.8.0 software was used to determine the core of the PPI network;a TCM drug-disease-target network was constructed to perform gene ontology(GO)functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis.Finally,Pymol software was used to perform molecular docking between the effective active components of Xiaoyao powder and the disease targets of depression.Results:The analyses in this study obtained 161 effective active components of Xiaoyao powder,2588 antidepressive targets of Xiaoyao powder(among which there were 6 core targets),2247 GO biological processes,and 179 KEGG pathways.Molecular docking showed that naringenin,licochalcone,luteolin,and quercetin in Xiaoyao powder could bind to the target proteins of depression well.Conclusion:The potential pharmacological mechanism of the antidepressive effect of Xiaoyao powder and its active components might be associated with the synergistic regulation of cell proliferation,immunoregulation,and inflammation induction.